Oncolytic adenoviruses (OAds) have shown great promise in cancer therapy, but their efficacy has been greatly limited by poor tumor selectivity and highly off-target liver sequestration. Herein, we generated a novel "stealth" and tumor-targeting OAd vector, M0-TMTP1, by inserting TMTP1 (NVVRQ), a tumor-homing peptide specifically targeting metastasis, into the hypervariable region 5 of hexon. M0-TMTP1 exhibits increased transduction of tumor cells in vitro. In vivo biodistribution of M0-TMTP1 in an intraperitoneal disseminated ovarian cancer model showed significantly reduced virus load in major organs but apparent aggregation in tumors. The tumor-to-liver ratio of M0-TMTP1 was nearly 5,000-fold higher than that of control adenovirus M0. Furthermore, we armed M0-TMTP1 with trunked BID, a mitochondrial apoptosis protein, to obtain M11. Combining M11 with cisplatin (DDP) could induce an intensive antitumor effect in vitro and in vivo. Moreover, this combination therapy showed higher biosafety. Taken together, our results suggest that M11 represents a tumor-targeting, efficacious, and relatively nontoxic virotherapeutic agent, and these findings might offer renewed hope for tumor management.
基金:
Technology Major Sub-Project [2018ZX10301402-002]; Technical Innovation Special Project of Hubei Province [2018ACA138]; National Natural Science Foundation of China [81772787, 82072889]; Fundamental Research Funds for the Central Universities [2019kfyXMBZ024]
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外文
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中科院(CAS)分区:
出版当年[2021]版:
大类|2 区医学
小类|2 区生物工程与应用微生物2 区遗传学2 区医学:研究与实验
最新[2025]版:
大类|3 区医学
小类|2 区生物工程与应用微生物3 区遗传学3 区医学:研究与实验
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出版当年[2020]版:
Q1GENETICS & HEREDITYQ1BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ2MEDICINE, RESEARCH & EXPERIMENTAL
最新[2024]版:
Q1GENETICS & HEREDITYQ2BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ2MEDICINE, RESEARCH & EXPERIMENTAL
第一作者单位:[1]Huazhong Univ Sci & Technol, Key Lab Minist Educ, Canc Biol Res Ctr, Wuhan, Peoples R China[2]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Obstet & Gynecol, Tongji Med Coll, Wuhan, Peoples R China
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol, Key Lab Minist Educ, Canc Biol Res Ctr, Wuhan, Peoples R China[2]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Obstet & Gynecol, Tongji Med Coll, Wuhan, Peoples R China[*1]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Obstet & Gynecol, Tongji Med Coll, Wuhan 430030, Hubei, Peoples R China
推荐引用方式(GB/T 7714):
Li Fei,Yuan Yuan,Dai Yun,et al.M11: A Tropism-Modified Oncolytic Adenovirus Arming with a Tumor-Homing Peptide for Advanced Ovarian Cancer Therapies[J].HUMAN GENE THERAPY.2022,33(5-6):262-274.doi:10.1089/hum.2021.247.
APA:
Li, Fei,Yuan, Yuan,Dai, Yun,Cheng, Teng,Cao, Heng...&Gao, Qinglei.(2022).M11: A Tropism-Modified Oncolytic Adenovirus Arming with a Tumor-Homing Peptide for Advanced Ovarian Cancer Therapies.HUMAN GENE THERAPY,33,(5-6)
MLA:
Li, Fei,et al."M11: A Tropism-Modified Oncolytic Adenovirus Arming with a Tumor-Homing Peptide for Advanced Ovarian Cancer Therapies".HUMAN GENE THERAPY 33..5-6(2022):262-274